Guidelines of Guidelines: Conservative, Pharmacological, and Surgical Management for Neurogenic Lower Urinary Tract Dysfunction

Neurogenic lower urinary tract dysfunction (NLUTD) encompasses a broad spectrum of neurological conditions affecting the lower urinary tract. Managing NLUTD requires a tailored approach focused on preserving kidney function and enhancing patients’ quality of life. Clinical guidelines provide valuable guidance for healthcare professionals, but discrepancies in recommendations arise among other factors due to limited high-quality clinical evidence. Prominent guidelines from organisations like the International Consultation of Incontinence, the European Association of Urology, the American Urological Association, and the National Institute for Health and Care Excellence offer varying recommendations for NLUTD management. This study reviews and summarizes the recommendations for conservative, pharmacological, and surgical management options across these guidelines.


Introduction
Neurogenic lower urinary tract dysfunction (NLUTD) encompasses a wide range of neurological conditions that impact the lower urinary tract.This diverse population experiences variations in causes, pathology onset, bladder dysfunction, and progression likelihood.

Methods
A thorough review of the conservative, pharmacological, and surgical management recommendations on NLUTD from the most prominent guidelines was undertaken.The most recent update of the seventh ICI (2021), EAU (2022), AUA (2021), and the NICE 2019 was reviewed and summarized.

Guidelines Recommendations
Behavioral Interventions are listed in Table 1.
Assisted bladder emptying: EAU and ICI guidelines contemplate Crede, Valsalva, and triggered reflex voiding (Table 1).However, EAU states that it would be considered only if urodynamically safe and warns of the risk of inducing autonomic dysreflexia and worsening pelvic floor weakness. 1Alongside treatment, EAU encourages patient education and surveillance techniques. 2 Pelvic floor muscle training: All guidelines agree on its use and suggest combining treatment with electromyographic biofeedback and/or electrostimulation, as dual therapy has been proven to be more effective. 3National Institute for Health and Care Excellence only advocates this technique in SCI (spinal cord injury) or MS, and the EAU recommend it only in MS patients.
Catheters and appliances are listed in Table 2.
Intermittent Self-Catheterization: EAU and ICI guidelines favor the use of ISC compared to indwelling catheters (IDCs) but differ in their choice of catheter and its indications.European Association of Urology highlights that aseptic intermittent self-catheterization (ISC) reduces urinary tract infections (UTI). 4American Urological Association also favors the use of ISC compared to IDC but stresses the risk of bias.It also mentions that ISC has been associated with worse quality of life than IDCs-observed in the SCI population. 5cross all guidelines, the importance of counseling the patients for ISC before botulinum toxin therapy is highlighted.
Indwelling catheters: All the guidelines suggest avoiding indwelling transurethral and suprapubic catheterization (SPC).However, ICI agrees to use it to an extent.If it is necessary, AUA makes a strong recommendation of SPC over an indwelling catheter.European Association of Urology stresses the increased chance of UTIs.International Consultation of Incontinence and AUA make recommendations against antibiotic prophylaxis.
Other considerations about catheter valve, urethral plugs, condom catheters, pads, and occlusive devices are described in the different guidelines (Table 2).
Pharmacotherapy guidelines are detailed in Table 3.
Anticholinergics: indicated across the four guidelines for patients with neurogenic detrusor overactivity (NDO).The EAU suggests employing antimuscarinics in combinations to maximize outcomes and advocates using oxybutynin, trospium, tolterodine, and propiverine due to their efficacy and long-term tolerability. 5Alongside these, in patients with SCI and MS experiencing NDO, Darifenacin, and Solifenacin 6 have been found to respond similarly.National Institute for Health and Care Excellence makes a weaker recommendation for their use in progressive brain conditions and draws on three main warnings: cognitive impairment, UTIs as reducing bladder emptying, and constipation.American Urological Association recommends antimuscarinics alone, or in combination with beta-3 adrenergic receptor agonists.It also recognizes the potential risk of cognitive impairment/dementia with its long-term use, therefore recommends shared patient decision making, as well as switching to other agents that do not cross the blood-brain barrier or combination of anticholinergics with alpha-blockers. 7Additionally, EAU adds alternative modes of administration as intravesical to minimize side effects. 8 agonists: recommended in isolation or combined with anticholinergics.However, EAU, ICI, and AUA mention conditional recommendation as monotherapy has shown inconclusive results. 9Cannabinoids: mentioned in EAU as an option.On ICI, the grade of recommendation is C.
Cholinergics: As mentioned by the EAU, bethanechol and distigmine enhance detrusor contractility and promote bladder emptying 10 and is neither is frequently used in clinical practice.The level of evidence for their use is 2b.
Alpha blockers: All 4 guidelines hold a slightly different stance (Table 3).
Duloxetine: not mentioned in any of the four guidelines.
Minimally invasive treatment options are listed in Table 4.
Electrostimulation: EAU mentions transcutaneous electrical nerve stimulation, dorsal genital nerve stimulation, transcranial magnetic stimulation, pudendal nerve electrical stimulation, interferential medium frequency current electrical stimulation, and neuromuscular electrical stimulation but they reserve their full support as there are limited reports proving efficacy.
Intravesical electrostimulation: EAU and ICI agree on their indication to improve the voiding phase 11 (Table 4).Unlike ICI, EAU also advocates for its application in patients with incomplete SCI or myelomeningocele.
Intravesical therapy: Recommended by EAU as an alternative route for antimuscarinics.International Consultation of Incontinence and NICE do not provide graded recommendations for alternative forms of antimuscarinic administration.Vanilloids and capsaicin have no current indication as their safety is not favorable. 12Cannabinoidsonly preclinical studies have detected its benefits. 13tulinum Toxin Injections Bladder: All four guidelines broadly agree on intradetrusor botulinum toxin injections for NDO.European Association of Urology, AUA, and NICE advocate its use in SCI and MS.In contrast, the ICI recommends it independent of the underlying neurological condition.To maximize effectiveness, EAU suggests alternating between brands (Botox® to Dysport®) in case of failure. 13As grade A evidence, AUA suggests continued efficacy with repeat injections.Due to weaker evidence in other neurologic conditions, AUA suggests it may be offered, for example in PD, CVA, and spina bifida, as well as those with persistent NDO after augmentation enterocystoplasty.
Pelvic floor: The guidelines do not mention pelvic floor injections for NLUTD.
Surgical management is detailed in Table 5.

Stress Urinary Incontinence
Before treatment selection, several factors should be considered, such as the severity of stress urinary incontinence (SUI), neurological impairment, possibility of progression, hand function, and ability to self-catheterize that needs to be present before the surgery according to EAU and ICI.At the same time, AUA suggests that only patients who can void on their own should be considered for sling surgery.
Urodynamics is strongly recommended.American Urological Association states that candidates should have acceptable storage parameters, and both ICI and AUA suggest using an occlusion catheter during UDS if necessary.European Association of Urology, AUA, and ICI report a higher incidence of de novo urgency in the neurogenic population after sling placement.

Urethral Slings
Synthetic slings: In female patients, NICE does not recommend its use due to the risk of urethral erosion.In contrast, the EAU considers retropubic and transobturator tapes as alternatives in selected patients.
The AUA suggests it should be avoided if there is a concern for future ISC and does not recommend its use as an occlusive sling.Optional for male patients, according to EAU.
Autologous slings: Procedure of choice in neurogenic female patients for EAU and NICE.They are stated as an option for males in EAU.International Consultation of Incontinence mentions that it is a preferable option with the same evidence of synthetic slings, and AUA suggests it should be used where an occlusive sling is considered.

Artificial Urinary Sphincter
The most common procedure in male SUI patients, with a high success rate. 14The complication rate is higher than in the non-neurogenic population. 15Therefore, adequate counseling/discussion with the patient is stressed across the guidelines.
European Association of Urology and ICI strongly recommend its use in male patients with neurogenic SUI.According to AUA, it is an option for selected patients (male and female).National Institute for Health and Care Excellence recommends its use only if an alternative procedure, such as an autologous fascial sling, is less likely to control incontinence (gender not mentioned).It recommends monitoring the upper tract with annual ultrasound on follow-up.American Urological Association stresses the risks of erosion with ISC, which may be reduced by bladder neck cuff location.
The laparoscopic and robot-assisted approach is promising and has increased its use in the female neurogenic population.Long-term surgical and patient-reported outcomes are still needed.European Association of Urology supports its use in selected female patients in experienced centers.American Urological Association states that a robotic approach is an attractive option.A transvaginal cuff is considered a poor option due to the high risk of infection.

Adjustable Continence Mechanisms (Pro-ACT /ACT)
In neurogenic population, it is considered experimental by AUA, and EAU mentions a lower cure rate with a higher complication rate when compared to non-neurogenic patients.Similarly, ICI states limited experience in neurogenic population.

Bulking
American Urological Association and ICI agreed that it showed modest efficacy and poor long-term outcomes.American Urological Association stresses the low-evidence studies in male neurogenic populations.European Association of Urology advocates early positive results with an early loss of continence in both females and male.Also, AUA emphasizes that it is unclear how ISC would impact the outcome.

Bladder Neck Closure
According to the ICI guidelines, it is performed mainly in children.It should be offered along with SPC, continent catheterizable stoma, or urinary diversion.It is considered an alternative in AUA for refractory cases or severe urethral pathologies.American Urological Association also stresses the importance of discussing the need for assisted reproduction.

Transurethral Resection of the Prostate
Careful selection is recommended across the guidelines.According to ICI and EAU, bladder outlet obstruction must be proven, and sphincter function assessed due to the high risk of de novo or persistent incontinence.International Consultation of Incontinence also states  that transurethral resection of the prostate is an option in patients with Parkinson's and mentions the lack of evidence to support the indication in patients with cerebrovascular diseases.Additionally, multiple system atrophy must be excluded due to the high risk of stress incontinence.

Bladder Neck Resection
It is recommended by EAU only if a sclerotic ring in the bladder neck is identified along with proven functional obstruction.Also, ICI states that there is a lack of evidence.It is not mentioned in AUA or NICE guidelines.

Urethrotomy
For urethral strictures, the treatment will be similar to the non-neurogenic population.A tailored stepwise approach is recommended, always considering the higher risk of needing intermittent catheterization.European Association of Urology recommends cold knife or neodymium/Yttrium Aluminum Garnet (YAG) contact laser at twelve o'clock.Urethroplasty should be considered in recurrent cases, according to ICI and EAU.

Sphincterotomy
It is recommended across the guidelines in appropriately selected male patients.It increases the effectiveness of bladder emptying, reducing UTI's, autonomic dysreflexia and vesicoureteral reflux. 16nternational Consultation of Incontinence stresses that the decrease of intravesical pressure is often unsatisfactory.According to AUA, ICI, and EAU, regular follow-up is required due to the risk of recurrence and additional treatment. 17erican Urological Association and EAU recommend it at the 12 o'clock position with electrocautery resection or neodymium, YAG laser incision in patients who experience reflex voiding and can maintain a condom catheter, have poor hand function, or are unwilling to perform ISC.

Bladder Neck Incision
It is contemplated by the EAU guidelines only for fibrosis at the bladder-neck level.It is not recommended in patients with detrusor hypertrophy as it causes thickening of the bladder neck.

Botulinum Toxin into the Urethral Sphincter
Considered for the treatment of detrusor sphincter dyssynergia by EAU and ICI as the efficacy reported is high with few adverse effects. 18However, it is stressed that its effect is temporary, the optimal dose and mode of injection are still unclear, and it is not licensed for this purpose.American Urological Association considers chemical sphincterotomy to have limited efficacy over time, and therefore, it is not recommended for routine management of DSD in NLUTD.

Urethral Stents
According to EAU, its effect is comparable with sphincterotomy with a shorter duration of surgery and hospital stay, and the continence relies on the bladder neck.International Consultation of Incontinence and EAU describe limiting factors such as costs, complications, and the need for reintervention.

Balloon Urethral Dilation
European Association of Urology declared no further reports since 1994; therefore, it is no longer recommended.

Denervation, Deafferentation, and Neuromodulation
Sacral Anterior Root Stimulation Produces detrusor and sphincter contraction; the latter relaxes faster, and "post-stimulus voiding" occurs. 19It requires a sacral deafferentation (dorsal rhizotomy) to control detrusor overactivity.It can also induce defecation or erection.Charcot spinal arthropathy is a potential long-term complication. 20According to EAU and ICI, candidates are patients with complete spinal cord injury above the implant location.American Urological Association states that it has promising outcomes.However, it is limited to investigational settings or specialty centers.

Percutaneous Tibial Nerve Evaluation
European Association of Urology, AUA, and ICI guidelines advocate its use but differ in their choice of delivery method 27-30).American Urological Association recommend its use in NLUTD patients with storage symptoms and spontaneous voiding, as it has shown benefits in MS, 21 PD, 22 and CVA 23 with isolated storage symptoms.It is currently approved for non-neurogenic OAB.

Sacral Neuromodulation
According to EAU and ICI, there is growing evidence, but it is still unclear which patients are most suitable.National Institute for Health and Care Excellence mentions it may be used in patients for whom conservative treatments have been unsuccessful.American Urological Association states that sacral neuromodulation (SNM) is not recommended for patients with complete spinal cord injury or spina bifida.However, it may be considered for storage symptoms in MS, CVA, and PD.There is also limited evidence for its use in other mixed neurologic diseases including cerebral palsy, acquired brain injuries, viral and vascular myelitis, encephalitis, central nervous system tumor, incomplete spinal cord injury, multisystem atrophy, and spinocerebellar atrophy.For voiding dysfunction, treatment may be considered in MS.Additionally, there must be consideration that in progressive disease, such as with MS, there may be concurrent worsening of NLUTD and loss of efficacy. 24

Major Surgery
Detrusor Myect omy/A uto-a ugmen tatio n As mentioned by EAU and ICI, it reduces detrusor overactivity and improves compliance.It was mainly used historically and in the pediatric population.

Bladder Augmentation
It is recommended across the 4 guidelines in patients refractory to less invasive therapies for detrusor overactivity and/or poor bladder compliance and small bladder capacity.National Institute for Health and Care Excellence specifies that its indication is for non-progressive neurological disorders.

Cystectomy
American Urological Association strongly recommends concurrent supra trigonal cystectomy or cystoprostatectomy at the time of urinary diversion in male NLUTD, as the delayed reoperation rate could be up to 50% due to empyema.The "Spence procedure" (vesicovaginal fistula) allows for drainage in female patients.European Association of Urology and NICE mentioned it as advisable to avoid pyocystitis.

Incontinent Urinary Diversion
Considered by EAU, ICI, and NICE in patients who are wheelchairbound or bed-ridden with untreatable incontinence, upper tract severely compromised with impaired renal function, lower urinary tract destruction, unable to catheterize, and in patients who refuse other therapy.American Urological Association considers it as a last resort in those patients where there has been a failure to provide safe and adequate storage function.Due to the high risk of long-term complications, these patients' continued long-term follow-up is imperative.

Ileovesicostomy
Considered by AUA for NLUTD patients unable to ISC.Counseling is essential due to the high risk of additional treatment or surgery.It is a reversible procedure.However, its drainage may be poor, with an increased risk of stones.

Undiversion
European Association of Urology considers that long-standing diversions may be successfully undiverted or an incontinent diversion changed to a continent one.However, ICI states that it is rarely indicated, requires meticulous planning, and has no evidence to date.

Other Surgical Procedures
European Association of Urology describes a series of procedures to restore continence and function, with some evidence of their use in the neurogenic population: 1) functional autologous sphincter using gracilis muscle and electrical stimulation 27 restoring control over the urethral closure; 2) bladder neck and urethra reconstruction; Young-Dees-Leadbetter and Kropp urethra lengthening; 3) covering the bladder with striated muscle rectus abdominis, latissimus dorsi.International Consultation of Incontinence considers bladder neck reconstruction mainly in the pediatric population combined with SPC or urinary diversion.However, due to insufficient evidence in neurogenic patients, ICI does not recommend latissimus dorsi/rectus abdominis.AUA states these procedures are investigational due to their infancy in development or lack of adequate data and suggests that it should only be performed in a well-designed clinical trial.

Conclusion
While guidelines agree broadly on standardized treatments, discrepancies emerge due to the scarcity of high-quality clinical evidence and the wide spectrum of neurogenic diseases included in a single guideline.Moreover, practices in different countries vary as well as the processes of production of the guidelines.Urgent research efforts are needed to strengthen the evidence base for NLUTD and improve patient care and outcomes.This will facilitate the development of more consistent and robust treatment recommendations across guidelines, ultimately benefiting NLUTD patients facing diverse challenges.

Table 2 .
Catheters and Appliances N/AImplanted catheters continue to be studied.Intraurethral valve pump device does not have an indication for NLUTD as of yet.AUA, American Urological Association; EAU, European Association of Urology; ICI, International Consultation of Incontinence; NDO, neurogenic detrusor overactivity; NICE, National Institute for Health and Care Excellence; NLUTD, neurogenic lower urinary tract dysfunction; UI, urinary incontinence; UTI, urinary tract infection.

Urology Research and Practice 2024;50(2):139-147 Ochoa et al. Comprehensive NLUTD Management
American Urological Association does not recommend surveillance cystoscopy in asymptomatic patients.European Association of Urology and ICI recommend special attention to patients with preoperative renal scars at higher risk of metabolic acidosis.